Monoclonal antibody (MAb) B72.3 binds to many human epithelial malignancies including breast, colon, ovarian and lung cancer. Radioiodinated B72.3 IgG can selectively bind to human colorectal carcinomas grown in athymic mice; the activity in the tumor rose for the first 2 days and remained constant over the 19 day period of study. Tumor-to-normal tissue ratios rose over this period of time with ratios of approximately 18:1 for liver, spleen and kidney at 7 days. B72.3 IgG was labeled with In-lll using four chelating agents: l-(p-isothiocyanato-benzyl)-DTPA (SCN-Bz-DTPA), MA-DTPA, CA-DTPA, and the SCN-Bz derivative of EDTA. Comparative biodistribution studies demonstrated that tumor uptake of radiolabel was very similar between the chelates (30% ID/g), however, a progressive accumulation of activity in the abdominal organs, predominantly in the liver, was seen with the MA-DTPA, CA- DTPA and SCN-Bz-EDTA chelate-antibody complexes. This uptake was very prominent with these chelate-MAb complexes but was virtually absent in the mice injected with B72.3SCN-Bz-DTPA. The high degree of selective binding of this MAb has led to the investigation of its potential as a radioimmunotherapeutic agent. Athymic mice bearing human colon carcinoma xenografts were injected with B72.3 IgG to assess the effect of the radiolabeled MAb on the tumor growth as well as potential toxic side effects in vital organs. In mice treated with the I-131 B72.3 IgG, a marked inhibition of the growth of the human colon carcinoma xenografts was noted. Toxicity was readily evident in the mice injected with the high-dose regimen (500 muCi), with confirmed bone marrow aplasia that proved lethal for 2 of 10 animals. Lower doses (300 muCi) resulted in a bone marrow suppression of approx. 50% of the cells, which proved to be non-lethal. The tumors in the treated mice showed extensive necrosis caused by the lethal dose of I-131- B72.3 that irreversibly damaged the cells.